Role of Annual Influenza Vaccination against Lung Cancer in Type 2 Diabetic Patients from a Population-Based Cohort Study

Abstract

Type 2 diabetes mellitus (DM) patients are at a higher risk for developing lung cancer due to immune dysfunction and chronic inflammation. They also have increased morbidity and mortality related to influenza, and it is recommended that they receive an annual influenza vaccination. In this study, we evaluate whether influenza vaccination could reduce the incidence of lung cancer in DM patients. This cohort study included DM patients (≥55 years old) between 1 January 2002 and 31 December 2012 by using the Taiwan Health Insurance Database. Cox proportional hazard regression method was used to compare the relation between the influenza vaccination and lung cancer incidence after adjusting for potential confounders. Sub-group analyses were done according to vaccination status (unvaccinated, total number of vaccinations: 1, 2–3, ≥4) and evaluated the dose-dependent effects on lung cancer events. Among 22,252 eligible DM patients, 7860 (35.32%) received an influenza vaccination and 67.68% (14392) did not receive an influenza vaccination. Lung cancer incidence was significantly lower in the vaccinated group versus the unvaccinated group (adjusted HR 0.77; 95% CI 0.62–0.95, p < 0.05). Significant protective effects were observed among male sex (adjusted HR 0.72; 95% CI 0.55–0.94, p < 0.05) and 55–64 year (adjusted HR 0.61; 95% CI 0.40–0.94, p < 0.05) and ≥75 year (adjusted HR 0.63; 95% CI 0.42–0.92, p < 0.05) age groups, respectively. A dose-dependent protective effect was noted with a significant protective effect in those that received ≥4 vaccinations (adjusted HR 0.42; 95% CI 0.29–0.61, p < 0.001). In sub-group analysis, elder patients with ≥65 years of age were significantly protected from ≥4 vaccinations (adjusted HR 0.37; 95% CI 0.23–0.62, p < 0.001 in 65–74 years and adjusted HR 0.31; 95% CI 0.15–0.66, p = 0.002 in ≥75 years group, respectively). Male sex with ≥4 vaccinations had a significantly lower risk of lung cancer (adjusted HR 0.35; 95% CI 0.21–0.57, p < 0.001). Patients with comorbid conditions that received ≥4 vaccinations were also protected, and was especially significant among those with CCI ≥ 3 (adjusted HR 0.38; 95% CI 0.18–0.80, p = 0.009) as compared to 1 and 2–3 vaccination groups, including those with hypertension (adjusted HR 0.35; 95% CI 0.22–0.57, p < 0.001). This population-based cohort study demonstrated that annual influenza vaccination significantly reduced the lung cancer risk in DM patients and specifically demonstrates that a higher number of vaccinations is related with a more protective effect. Whether this is due to vaccine booster effects on anti-tumor immune regulation among DM patients still needs to be explored.

Effect of Annual Influenza Vaccination on the Risk of Lung Cancer Among Patients With Hypertension: A Population-Based Cohort Study in Taiwan

“…The dose-dependent protective effect of the influenza vaccination for all ages and both sexes (significantly for individuals aged >75 years) was also identified in our other studies [ 24 , 25 ]. Influenza vaccination-related immunomodulation might explain this phenomenon.…”

“…Thus, the Taiwanese government has recommended an annual government-funded influenza vaccination for high-risk individuals since 1998 [ 23 ]. In our previous studies, we observed that influenza vaccination could protect patients with chronic lung disease [ 24 ] and diabetes mellitus [ 25 ] from the risk of lung cancer. Whether influenza vaccination reduces the risk of lung cancer among patients with hypertension has yet to be determined.…”

Influenza vaccination is associated with lower risk of renal cell carcinoma among chronic kidney disease patients: a population-based cohort study

“…Indeed, influenza vaccination has been shown to reduce the risk for pneumonia-/influenza-related hospitalizations and mortality [ 61–63 ]. Our previous study also revealed a reduction in the risk of lung cancer with influenza vaccination among diabetic patients [ 64 ]. Another study indicated that the frequency and severity of influenza infections were positively related to the risk of lung cancer events [ 65 ], however, the relation between many other solid cancers and influenza events is still unclear.…”

Influenza vaccination and risk of atrial fibrillation in patients with gout: A nationwide population-based cohort study

“…In 1995, Taiwan’s National Health Insurance (NHI) program was established to provide the residents of Taiwan with comprehensive health insurance. This program currently covers more than 98% of the population in Taiwan ( Luo et al, 2020 ; Chen et al, 2021 ; Zheng et al, 2021 ). In this study, the statistical characteristics of the sample group were similar to those of the general population.…”